PMID- 17702822
OWN - NLM
STAT- MEDLINE
DCOM- 20080110
LR  - 20191210
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 584
IP  - Pt 2
DP  - 2007 Oct 15
TI  - Ca2+-dependent ATP release from A549 cells involves synergistic autocrine 
      stimulation by coreleased uridine nucleotides.
PG  - 419-35
AB  - Extracellular ATP is a potent surfactant secretagogue but its origin in the 
      alveolus, its mechanism(s) of release and its regulatory pathways remain unknown. 
      Previously, we showed that hypotonic swelling of alveolar A549 cells induces 
      Ca(2+)-dependent secretion of several adenosine and uridine nucleotides, 
      implicating regulated exocytosis. In this study, we examined sources of Ca(2+) 
      for the elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) evoked by 
      acute 50% hypotonic stress and the role of autocrine purinergic signalling in 
      Ca(2+)-dependent ATP release. We found that ATP release does not directly involve 
      Ca(2+) influx from extracellular spaces, but depends entirely on Ca(2+) 
      mobilization from intracellular stores. The [Ca(2+)](i) response consisted of 
      slowly rising elevation, representing mobilization from thapsigargin 
      (TG)-insensitive stores and a superimposed rapid spike due to Ca(2+) release from 
      TG-sensitive endoplasmic reticulum (ER) Ca(2+) stores. The latter could be 
      abolished by hydrolysis of extracellular triphospho- and diphosphonucleotides 
      with apyrase; blocking P2Y(2)/P2Y(6) receptors of A549 cells with suramin; 
      blocking UDP receptors (P2Y(6)) with pyridoxal phosphate 
      6-azophenyl-2',4'-disulfonic acid (PPADS); emptying TG-sensitive stores 
      downstream with TG or caffeine in Ca(2+)-free extracellular solution; or blocking 
      the Ca(2+)-release inositol 1,4,5-triphosphate receptor channel of the ER with 
      2-aminoethyldiphenylborinate. These data demonstrate that the rapid [Ca(2+)](i) 
      spike results from the autocrine stimulation of IP(3)/Ca(2+)-coupled P2Y, 
      predominantly P2Y(6), receptors, accounting for approximately 70% of total 
      Ca(2+)-dependent ATP release evoked by hypotonic shock. Our study reveals a novel 
      paradigm in which stress-induced ATP release from alveolar cells is amplified by 
      the synergistic autocrine/paracrine action of coreleased uridine and adenosine 
      nucleotides. We suggest that a similar mechanism of purinergic signal propagation 
      operates in other cell types.
FAU - Tatur, Sabina
AU  - Tatur S
AD  - Centre hospitalier de l'Universite de Montreal - Hotel-Dieu, 3850 Saint-Urbain, 
      Montreal, Quebec, Canada.
FAU - Groulx, Nicolas
AU  - Groulx N
FAU - Orlov, Sergei N
AU  - Orlov SN
FAU - Grygorczyk, Ryszard
AU  - Grygorczyk R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070816
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hypotonic Solutions)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (P2RY2 protein, human)
RN  - 0 (Purinergic P2 Receptor Antagonists)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Receptors, Purinergic P2Y2)
RN  - 0 (Uracil Nucleotides)
RN  - 0 (purinoceptor P2Y6)
RN  - 149017-66-3 (pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid)
RN  - 3G6A5W338E (Caffeine)
RN  - 5V5IOJ8338 (Pyridoxal Phosphate)
RN  - 6032D45BEM (Suramin)
RN  - 67526-95-8 (Thapsigargin)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.6.1.5 (Apyrase)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Apyrase/pharmacology
MH  - *Autocrine Communication
MH  - Caffeine/pharmacology
MH  - Calcium/*metabolism
MH  - *Calcium Signaling/drug effects
MH  - Calcium-Transporting ATPases/antagonists & inhibitors/metabolism
MH  - Cell Line, Tumor
MH  - Endoplasmic Reticulum/drug effects/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Epithelial Cells/drug effects/*metabolism/pathology
MH  - Humans
MH  - Hydrolysis
MH  - Hypotonic Solutions
MH  - Inositol 1,4,5-Trisphosphate Receptors/antagonists & inhibitors/metabolism
MH  - Lung Neoplasms/*metabolism/pathology
MH  - Osmotic Pressure
MH  - *Paracrine Communication
MH  - Purinergic P2 Receptor Antagonists
MH  - Pyridoxal Phosphate/analogs & derivatives/pharmacology
MH  - Receptors, Purinergic P2/metabolism
MH  - Receptors, Purinergic P2Y2
MH  - Suramin/pharmacology
MH  - Thapsigargin/pharmacology
MH  - Time Factors
MH  - Uracil Nucleotides/*metabolism
PMC - PMC2277166
EDAT- 2007/08/19 09:00
MHDA- 2008/01/11 09:00
PMCR- 2008/10/15
CRDT- 2007/08/19 09:00
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2008/01/11 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
PHST- 2008/10/15 00:00 [pmc-release]
AID - jphysiol.2007.133314 [pii]
AID - 10.1113/jphysiol.2007.133314 [doi]
PST - ppublish
SO  - J Physiol. 2007 Oct 15;584(Pt 2):419-35. doi: 10.1113/jphysiol.2007.133314. Epub 
      2007 Aug 16.